Abstract:
:This study evaluates the association between the long noncoding RNA GAS5 levels and the anti-proliferative effect of the glucocorticoid (GC) methylprednisolone (MP) alone and in combination with rapamycin in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. The effect of MP, rapamycin, and MP plus rapamycin was determined in 17 healthy donors by labelling metabolically active cells with [methyl-3H] thymidine and the expression levels of GAS5 gene were evaluated by real-time RT-PCR TaqMan analysis. We confirmed a role for GAS5 in modulating GC response: poor responders presented higher levels of GAS5 in comparison with good responders. Interestingly, when PBMCs were treated with the combination of rapamycin plus MP, the high levels of GAS5 observed for each drug in the MP poor responders group decreased in comparison with rapamycin (P value = 0.0134) or MP alone (P value = 0.0193). GAS5 is involved in GC resistance and co-treatment of rapamycin with GCs restores GC effectiveness in poor responders through the downregulation of the long noncoding RNA. GAS5 could be considered a biomarker to personalize therapy and a novel therapeutic target useful for the development of new pharmacological approaches to restore GC sensitivity.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Lucafò M,Bravin V,Tommasini A,Martelossi S,Rabach I,Ventura A,Decorti G,De Iudicibus Sdoi
10.1111/1440-1681.12572subject
Has Abstractpub_date
2016-06-01 00:00:00pages
602-5issue
6eissn
0305-1870issn
1440-1681journal_volume
43pub_type
杂志文章abstract::1. Skeletal muscle oxidative function and metabolic gene expression are co-ordinately downregulated in metabolic diseases such as insulin resistance, obesity and Type 2 diabetes. Altering skeletal muscle metabolic gene expression to favour enhanced energy expenditure is considered a potential therapy to combat these d...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2009.05311.x
更新日期:2010-03-01 00:00:00
abstract::1. Deposition of β-amyloid (Aβ) peptide is a defining pathological hallmark of Alzheimer's disease (AD) and is involved in memory impairment. Evidence suggests that activation of an extracellular signal-regulated kinase (ERK) pathway is related to Aβ accumulation. Thus, the aim of the present study was to investigate ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2012.12000.x
更新日期:2012-10-01 00:00:00
abstract::1. Neuropeptide Y (NPY) is colocalized with catecholamines in central regions involved in blood pressure regulation and exerts depressor responses in the nucleus tractus solitarius (NTS). Ageing is accompanied by a decline in baroreflex function and a reduction in NPY concentrations in some brain areas. The present st...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb01801.x
更新日期:1997-02-01 00:00:00
abstract::1. Studies using animal experimental models have suggested that the beta2-adrenoceptor is uncoupled in association with alterations in the expression of G-protein-coupled receptor kinases (GRK) 2/3 in heart failure. However, the functional expression of the components of this pathway in human disease has not been full...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03625.x
更新日期:2002-03-01 00:00:00
abstract::1. Ambulatory monitoring provides a unique opportunity for studying the temporal relationships between lifestyle factors and blood pressure (BP). These include physical activity, mental activity, environmental stressors, substances ingested for pleasure such as smoking, alcohol and caffeine, and nutrition. 2. Changes ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1995.tb01986.x
更新日期:1995-03-01 00:00:00
abstract::1. The present brief review examines some of the new developments in the area of circadian rhythm research. 2. The discovery of the mouse clock and m-per genes and their similarity to other clock genes like per and tim has provided new insight into the control of rhythms in vertebrates. In mice, these genes are expres...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1998.tb02168.x
更新日期:1998-10-01 00:00:00
abstract::1. The aim of the present study was to determine the relationship between plasma levels of nitrite/nitrite (NO(x)) and brachial flow-mediated dilation (FMD) in healthy young men and women. 2. Brachial artery FMD was assessed non-invasively using high-resolution ultrasound in 36 young men and women (21 +/- 3 years; 18 ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04715.x
更新日期:2007-12-01 00:00:00
abstract::1. Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease. The aim of the present study was to identify the gene mutation in a Chinese family with LQTS and investigate the functional changes associated with the mutation. 2. Polymerase chain reaction and DNA sequencing were used to screen for the KCN...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2009.05150.x
更新日期:2009-08-01 00:00:00
abstract::According to Guyton's model, impaired renal sodium excretion plays a key role in the increased salt sensitivity of blood pressure (BP). Several factors contribute to impaired renal sodium excretion, including the sympathetic nervous system, the renin-angiotensin system and aldosterone. Accumulating evidence suggests t...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12177
更新日期:2013-12-01 00:00:00
abstract::1. Pharmacological compounds that release nitric oxide (NO) have been useful tools in the evaluation of the broad role of NO in physiopathology and therapeutics. The present study compared the pharmacokinetics and pharmacodynamics of enalapril and an NO-releasing enalapril molecule (NCX899) in conscious male beagles. ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04559.x
更新日期:2007-04-01 00:00:00
abstract::Urapidil had blocking activity on alpha 1-adrenoceptors in the rat isolated caudal artery (pA2 congruent to 7) and in the anaesthetized rat. Urapidil had no clonidine like agonistic activity on alpha 2-adrenoceptors in preparations of the guinea-pig ileum (prejunctional) or dog saphenous vein (post-junctional). Urapid...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00289.x
更新日期:1984-07-01 00:00:00
abstract::1. The haemodynamic and metabolic effects of oral intake of approximately 30 mg/kg per day N-nitro-L-arginine (NOLA) were examined in sham and adrenocorticotrophin (ACTH, 0.5 mg/kg per day) treated conscious Sprague-Dawley rats (n = 33). 2. NOLA administration produced an increase in systolic blood pressure of 24 +/- ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1992.tb00403.x
更新日期:1992-10-01 00:00:00
abstract::1. This study was designed to elucidate the effects of guar gum, a dietary fibre, on changes in prostanoid contents induced by 1,2-dimethylhydrazine, a carcinogenic agent, in rat colonic mucosa. 2. Prostanoid contents were determined using high performance liquid chromatography; five prostanoids, namely 6-keto-prostag...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1995.tb01928.x
更新日期:1995-10-01 00:00:00
abstract::1. Endothelium-derived nitric oxide (NO), a major modulator of vascular tone, is synthesized from the terminal guanidino nitrogen of L-arginine. This reaction is inhibited by analogues of L-arginine, such as N-nitro-L-arginine methyl ester (L-NAME). Many of the biological effects of NO are mediated by the second messe...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::1. The present experiments were performed in order to study the role of the sarcoplasmic reticulum (SR) in the altered action potential and contraction of ventricular myocardium obtained from myopathic Syrian hamster and explanted human hearts (n = 8). The hamsters included age-matched healthy hamsters (F1B; n = 18), ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03820.x
更新日期:2003-04-01 00:00:00
abstract::1. Kynurenine aminotransferase catalyzes the conversion of kynurenine to kynurenic acid, an endogenous antagonist of excitatory amino acid receptors. The kynurenic acid content and kynurenine aminotransferase activity was measured in micro-dissected regions of spontaneously hypertensive rats (SHR) and their normotensi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02460.x
更新日期:1994-11-01 00:00:00
abstract::1. The effect of pretreatment with nifedipine on naloxone-stimulated corticotrophin-releasing hormone (CRH)-induced adrenocorticotrophin (ACTH) release in humans was investigated. The mean peak plasma ACTH and cortisol levels and the mean peak change in cortisol levels from basal were significantly lower in the nifedi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01451.x
更新日期:1991-05-01 00:00:00
abstract::1. There is controversy regarding plasma catecholamine levels in patients with hypertrophic cardiomyopathy (HCM) and few data exist on serial plasma catecholamine measurements during exercise. The present study determined whether cardiovascular and plasma catecholamine responses to exercise were altered in patients wi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1998.tb02177.x
更新日期:1998-12-01 00:00:00
abstract::1. Oxidative stress plays a role in senescence-associated organ deterioration. This is supported by the beneficial effects of anti-oxidants against ageing-related organ damage, although their role in cardiac ageing has not been elucidated. 2. The aim of the present study was to examine the impact of cardiac-specific o...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04540.x
更新日期:2007-01-01 00:00:00
abstract::1. Adenosine A(1) receptors (A(1)R) play an important role in cardioprotection against hypoxic damage and the opening of mitochondrial permeability transition pores (MPTP) is central to the regulation of cell apoptosis and necrosis. However, it is still unclear whether A(1)R open MPTP in hypoxic cardiomyocytes. 2. The...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2009.05300.x
更新日期:2010-03-01 00:00:00
abstract::1. Landrace swine were identified as malignant hyperpyrexia susceptible (MHS) or control by the contracture responses of gracilis muscle fibre bundles to 3% halothane, 2 mmol/l caffeine and 80 mmol/l KCl. The effects of calmodulin-antagonist drugs on the contractile behaviour of control and MHS preparations were inves...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01103.x
更新日期:1988-06-01 00:00:00
abstract::1. The distribution of binding sites for [125I]-labelled endothelin-1 ([125I]-ET-1) and [125I]-labelled sarafotoxin S6B ([125I]-SRT) was visualized in rat tissues using in vitro autoradiography. 2. A high density of endothelin-1 (ET-1) binding was found in the heart. In the kidney, ET-1 binding occurred in association...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01485.x
更新日期:1991-07-01 00:00:00
abstract::1. Irinotecan (also known as CPT-11) is a water soluble, semi-synthetic analogue of 20(S)camptothecin (CPT) with promising activity against a range of tumour types. 2. As with all other active analogues of CPT, irinotecan causes cell toxicity by stabilizing a ternary complex between the nuclear enzyme topoisomerase I ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1996.tb01158.x
更新日期:1996-10-01 00:00:00
abstract::1. Mechanisms involved in the plasma extravasation observed following thermal injury of rat dorsal skin were investigated. 2. Heat applied to the dorsal skin of anaesthetized rats by a temperature-controlled skin heater (1 cm diameter) for 5 min induced temperature-dependent plasma protein extravasation at 48-48.5 deg...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb02705.x
更新日期:1997-11-01 00:00:00
abstract::1. Oxygen (O2) transfer from the blood to tissues is a function of the red blood cell (RBC) O2 saturation (SO2), the plasma O2 content being negligible. Under conditions of increased tissue O2 demand, the SO2 of arterial blood does not change appreciably (97%); however, the SO2 of mixed venous blood, equal to that of ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2000.03383.x
更新日期:2000-12-01 00:00:00
abstract::1. Using the electromagnetic flow probe and the radioactive microsphere technique, systemic and regional haemodynamic variables were measured in conscious normotensive and hypertensive rabbits. The rabbits were made hypertensive by unilateral nephrectomy combined with cellophane-wrapping of the remaining kidney and sy...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1981.tb00155.x
更新日期:1981-05-01 00:00:00
abstract::Receptors for parathyroid hormone (PTH) in the renal tubule are coupled to adenylate cyclase stimulation. PTH causes a rise in urinary cAMP by leakage from adenylate cyclase stimulation. PTH causes a rise in urinary cAMP by leakage from cells of the proximal convoluted tubule. The effects of alpha-adrenergic agonists ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00287.x
更新日期:1984-07-01 00:00:00
abstract::1. The aims of the present study were to investigate the pharmacological effects of quercetin on wild-type (WT) and mutant (I502A) human (h) Kv1.5 channel currents (I(kur)) and to identify whether mutation in the S6 segment is critical to activation of I(kur) by quercetin. 2. Experiments were performed on WT and site-...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.05061.x
更新日期:2009-02-01 00:00:00
abstract::Capillary permeability (CP) is elevated in late normal pregnancy, when compared to postpartum values. In women with pregnancy associated hypertension (PAH), pregnancy CP levels are not different from postpartum and are less than in normal pregnancy. These changes in capillary permeability are not explained by alterati...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1983.tb00210.x
更新日期:1983-05-01 00:00:00
abstract::1. Sulfur dioxide (SO(2) ) has recently been found to have various biological effects on the cardiovascular system. The present study was designed to explore the effects of SO(2) derivatives on the L-type calcium current (I (Ca, L) ) in isolated rat ventricular cardiomyocytes. 2. A Langendorf system was used to dissoc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2011.05528.x
更新日期:2011-07-01 00:00:00